Febrile seizure is a disease that has a high incidence rate of approximately 8% in infants. A main symptom of febrile seizure is known as a continuation of generalized convulsions for 1 to 5 minutes while suffering a fever at or over 38° C. caused by a viral or bacterial infection such as a cold, or microbism. Most cases of febrile seizure that have an onset of between 6 months after birth and around 5 years old cure by the time when the patient turns 6 years old. In many cases, febrile seizure does not require active treatment. Therefore, febrile seizure is considered, in principle, as a benign disease.
However, among patients whose onset of febrile seizure was under the age of one, other than the patients of the benign disease which cease as a regular febrile seizure, there are some patients who suffer from convulsions continuously even after turning 6 years old, and there are some patients who are patients of Dravet syndrome (previously called “Severe Myoclonic Epilepsy in Infancy; SMEI”), which are patients of an intractable epilepsy disease.
The patients of Dravet syndrome are triggered in the onset of convulsions under the age of one. An average age of the onset of convulsions for patients of Dravet syndrome is 4 months to 6 months after birth. An incipient seizure of convulsion for a patient of Dravet syndrome is generally a systemic or a unilateral tonic-clonic or clonic convulsion, and during infancy, may lead to status epilepticus. Moreover, this convulsion seizure is easily induced by fever or bathing.
Conventionally, febrile seizure was diagnosed and treated by a general pediatrician or a family doctor, and Dravet syndrome is also diagnosed based on clinical symptoms characteristic of Dravet syndrome such as convulsion seizure or the like. However, by the time the patients of Dravet syndrome turn two to three years old, that is around when the clinical symptoms of Dravet syndrome have all appeared, these patients would have suffered repetitive convulsions many times and would often have had experienced critical conditions such as status epilepticus or the like. Hence, it is necessary to develop a diagnosis method that enables detection of Dravet syndrome in its possible earliest stage by a general pediatrician or family doctor, who is engaged in primary medical care. Detection of Dravet syndrome at an earlier stage would allow for the patent to see an epilepsy specialist in advance, which would allow for preventing the patient from reaching a critical condition.
Recently, it has been reported that 30% to 80% of Dravet syndrome patients find missense mutation (mutation causing a substitution of an amino acid) and nonsense mutation (mutation causing protein synthesis to stop in an incomplete state) on a SCN1A gene that encodes a voltage-gated sodium ion channel NaV1.1 α-subunit type 1 (see Non Patent Literature 1 and 2). From such a point in view, attempts have been made to examine abnormalities in the SCN1A gene to diagnose Dravet syndrome on the basis of genes.
For example, Patent Literatures 1 to 4 disclose that mutation of the SCN1A gene is related to SMEI. Moreover, Patent Literatures 1 to 4 disclose that SMEI can be diagnosed by use of the mutation of the SCN1A gene as an indicator.
More specifically, Patent Literature 1 discloses the diagnosis of SMEI by assessing a plurality of mutations on the SCN1A gene that relate to SMEI, as a whole.
Patent Literature 2 discloses the diagnosis of SMEI performed by detecting a presence of a mutation that frequently occurs on the SCN1A gene of a nerve that is affected by SMEI.
Patent Literatures 3 and 4 disclose a method of diagnosing epilepsy syndromes including SMEI and syndromes associated with SMEI, by detecting a change in the SCN1A gene and confirming whether that change is known as being related to SMEI or a syndrome associated with SMEI or is known as not being related to SMEI or a syndrome associated with SMEI.